Laser lipolysis has a skin tightening effect by heating the deep dermis, in addition to the removal of fat tissues. The 1444-nm neodymium:yttrium–aluminum–garnet (Nd:YAG) laser has been expected to be more effective and safe for laser lipolysis, due to higher affinity to fat and water, than 1064-nm and 1320-nm wavelengths. The purpose of this study was to evaluate the skin tightening effect of the 1444-nm Nd:YAG laser through in vivo guinea pig models. The 1444-nm Nd:YAG laser was used to irradiate shaved dorsal skin of the guinea pigs and compared with controls (no power, only tunneling). Immediately, 1 week, 1 month and 3 months after laser administration, full-thickness skins were harvested and to evaluate dermal thickness, collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, using hematoxylin–eosin, Masson-trichrome, Verhoeff's stain and Alcian blue stain. Dermal thickness showed an increase with time in all groups. In collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, the treatment groups were higher than those of the control group, overall. Our study showed that the 1444-nm Nd:YAG laser appeared to be effective for the skin tightening effect in in vivo guinea pig models. The 1444-nm Nd:YAG laser can be used for skin tightening, as well as reduction of fat tissues.